The present invention relates to a process for the preparation of aromatic or heteroaromatic sulphonyl chlorides by diazotization of amino-substituted aromatics or heteroaromatics and decomposition of the resulting diazonium salts in the presence of sulphur dioxide.
Aromatic sulphonyl chlorides are important intermediates for crop-protection products, pharmaceuticals and dyes. From Chem. Ber. 90, 1957, p. 841, it is known to prepare this class of compound by diazotization of the corresponding aromatic amines with aqueous sodium nitrite solutions and decomposition of the diazonium salts in solutions of sulphur dioxide, copper salts and acetic acid. Where appropriate, a water-immiscible organic solvent is also added so that the reaction mixture is two-phase. This process does, however, have a number of disadvantages. For example, the yields are unsatisfactory in many cases. While electron-withdrawing groups, as further substituents in the diazonium salts, have a favourable effect on the yield and the reaction rate, the use of diazonium salts, which carry electron-donating substituents, leads only to low yields. In addition, when the reaction is carried out on an industrial scale, large amounts of wastewater which contains copper and acetic acid are formed. The processing and disposal of such wastewater is costly and is not possible using an economic process. If diazonium salts containing electron-withdrawing substituents on the aromatic ring are used, such as dinitrobenzene-diazonium chlorides, it is in some circumstances also possible to carry out the process without the copper salts as catalyst. Although the yields in this case are not much lower than in the presence of the catalyst, the reaction rate does drop considerably.
German Offenlegungsschrift 2,308,262 discloses a further process for the preparation of aromatic sulphonyl chlorides in which the sulphur dioxide is used in the form of alkali metal hydrogen sulphite in the presence of copper or copper salts. The addition of acetic acid or other organic solvents is not necessary here, the aromatic diazonium salts are used in strong hydrochloric acid solution. According to EP-A-0,059,241, the reaction of the aqueous diazonium salt solution with sulphur dioxide is carried out in the presence of a solvent which is immiscible or miscible only to a limited extent with water, and copper salts as catalyst, and subsequently the reaction mixture is treated with an oxidizing agent.
Although these processes avoid the problem of wastewater containing acetic acid being produced, as a result of the diazotization of the anilines in an aqueous medium and the use of dilute aqueous diazonium salt solutions in the reaction with the sulphur dioxide in the presence of copper, large amounts of wastewater containing copper salts are again formed. Furthermore, the space-time yield of these processes is unsatisfactory as a result of the use of dilute aqueous diazonium salt solution and the large volumes which arise as a result. In addition, the handling of the diazonium salt solutions requires specific precautionary measures because of the decomposability of the diazonium salts. For example, these solutions must be handled at low temperatures around 0xc2x0 C. and be processed quickly in order to limit yield losses in industrial operation.
All of the abovementioned processes have the common disadvantage that the conversion of the anilines into the corresponding aromatic sulphonyl chlorides takes place in two stages. In the first stage, the diazotization of the aniline with aqueous sodium nitrite solution takes place, and in the second stage, the decomposition of the diazonium salt in the presence of sulphur dioxide or alkali metal hydrogen sulphite, a copper compound and, where appropriate, an organic solvent.
There is therefore a need for a process which permits the preparation of aromatic or heteroaromatic sulphonyl chlorides from the parent anilines or amino-substituted pyridines in a simple manner with a high chemical yield, a high space-time yield, coupled with the formation of only a small amount of wastewater.
The invention provides a process for the preparation of aromatic or heteroaromatic sulphonyl chlorides of the general formula I 
in which
X may be a C or N,
R1 may be fluorine, chlorine, bromine, nitro, methoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, C1-C4 alkyl or phenyl, and
R2 may be H, fluorine, chlorine, bromine, OH or C1-C4 alkyl, by diazotization of the compounds of the general formula II 
in which
X, R1 and R2 are as defined for formula (I), and decomposition of the resulting diazonium salts in the presence of sulphur dioxide and a copper catalyst, characterized in that the compounds of the formula (II) are treated, in a mixture with one or more organic solvents, sulphur dioxide and a copper catalyst, with hydrogen chloride and alkyl nitrite at temperatures of from xe2x88x9220 to +60xc2x0 C.
If, in the formulae (I) and (II), R1 and R2 are C1-C4 alkyl, these alkyl radicals may be straight-chain or branched, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-butyl may be used.
In the formulae (I) and (II), R1 is preferably fluorine, chlorine, bromine, nitro, methoxy, trifluoromethoxy, methyl or ethyl, and R2 is preferably hydrogen, fluorine, chlorine, bromine, methyl or ethyl.
In the formulae (I) and (II), R1 is particularly preferably fluorine, chlorine, bromine, nitro or trifluoromethoxy, and R2 is particularly preferably hydrogen.
If the compounds of the formula (II) are substituted anilines, i.e., X is C, the substituents R1 and R2 are then preferably in the 2- and/or 4-position relative to the amino radical. If the compounds of the formula (II) are substituted amino-pyridines, i.e., X is N, then the amino radical is preferably in the 3-position, and the substituents R1 and R2 are preferably in the 2- and/or 6-position.
Specific examples of compounds of the formula (II) on which the process of the invention can be used advantageously are 2-nitroaniline, 4-nitroaniline, 2-trifluoromethoxyaniline and 3-amino-2-chloropyridine. These compounds are available commercially.
Suitable organic solvents for the process of the invention are those which are essentially inert under the reaction conditions and at least partly dissolve the starting materials of the formula (I), sulphur dioxide, hydrogen chloride and the copper catalyst. Examples of such solvents are aromatic hydrocarbons, alcohols, ethers, halogenated hydrocarbons, sulphoxides and sulphones. Such solvents can be used individually or as mixtures of two or more solvents.
Preference is given to using aromatic hydrocarbons, for example, toluene, xylene, ethyl benzene, halogenated hydrocarbons, such as methylene chloride, 1,2-dichloroethane, chlorobenzene or dichlorobenzene, alcohols, such as methanol, ethanol, 1-propanol, 2-propanol, isomeric butanols, isomeric pentanols or isomeric hexanols, or ethers, such as methyl tert-butyl ether, tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether or polyethylene glycol dimethyl ether as solvent.
Such solvents can also be used in mixtures with water. The addition of water can in some cases favour the solubilities of the starting materials. Here, it is insignificant whether such mixtures form one or two liquid phases. However, the addition of water is limited to small amounts of from 0.1 to 0.5 part by weight, based on the total amount of the organic solvent, depending on the process.
The amount of solvent is such that readily stirrable solutions or suspensions are obtained and, depending on its solubilizing power for the starting components, is advantageously 1-20 parts by weight, preferably 1.5-10 parts by weight, based on the compounds of the formula (II).
In order to obtain the highest possible yields of sulphonyl chlorides of the formula (I), it is expedient to use at least equimolar amounts of sulphur dioxide based on the compounds of the formula (II); it is, however, generally advisable to use a 1-8 molar, preferably 1-6-molar, particularly preferably 1.5-5 molar, excess of sulphur dioxide.
It is possible to add all of the sulphur dioxide to be used according to the invention to the reaction mixture prior to the treatment of the reaction mixture with alkyl nitrite. It can, however, also be introduced initially in partial amounts and the remainder added at the same time as the alkyl nitrite.
A suitable copper catalyst is elemental copper and also copper compounds. The copper in the copper catalyst to be used can have the valencies 0, 1, 2 or 3, preferably 1 or 2. Possible use forms are copper salts of inorganic and organic acids, for example, copper fluoride, copper chloride, copper bromide, copper sulphate, copper nitrate, and also the copper oxides, the copper salts of organic acids, such as copper acetate, copper citrate and copper stearate, and copper complexes, such as copper acetylacetonate and N,Nxe2x80x2-disalicylidene ethylenediamine copper (II). The copper catalyst can be used in solution, preferably in alcoholic and, in particular, in methanolic, solution.
The copper catalyst is used here in an amount of 0.001-0.5 mol, preferably 0.005-0.1 mol, per mole of the compound of the formula (II).
Hydrogen chloride is expediently used in gaseous form. It can be fed in at the same time as the alkyl nitrite. It is, however, also possible to add all or some of the hydrogen chloride to the reaction mixture before the latter is treated with alkyl nitrite. The amount of hydrogen chloride is at least equimolar based on the aniline or the amino-substituted pyridine of the formula (II). Preferably, hydrogen chloride is used in an amount of 1-4 equivalents, particularly preferably 1-2 equivalents, based on the compound of the formula (II).
The alkyl nitrite used is usually methyl nitrite, ethyl nitrite or isopropyl nitrite. Preference is given to using methyl nitrite. Methyl nitrite can be prepared by reacting alkali metal nitrites with methanol in the presence of strong acids in a simple manner. Since it is gaseous under the working conditions, it is metered in as a gas at a rate which the progress of the reaction allows.
Here, the alkyl nitrite is used at least in equivalent amounts, preferably in amounts of 1-3 equivalents, particularly preferably 1-1.5 equivalents, based on the compounds of the formula (II), to achieve high yields. However, a greater excess of alkyl nitrite does not impair the result of the reaction.
The reaction temperature for the process of the invention can vary between xe2x88x9220 and +60xc2x0 C. The process is preferably carried out at a temperature of from xe2x88x9210 to +40xc2x0 C., particularly preferably from xe2x88x9210 to +30xc2x0 C.
In a preferred embodiment of the process of the invention, the compound of the formula (II), the organic solvent and the copper catalyst are firstly added, then, with adjustment to a temperature in the range from xe2x88x9220 to +60xc2x0 C., some of the hydrogen chloride and the sulphur dioxide are added, and then further hydrogen chloride and the alkyl nitrite are metered in.
The process of the invention for the preparation of aromatic or heteroaromatic sulphonyl chlorides differs from the processes known hitherto by virtue of the fact that the diazotization of the anilines or amino-substituted pyridines and the decomposition of the resulting diazonium salts are not carried out in two separate stages, but at the same time in a single stage, and by virtue of the fact that the reaction can be carried out successfully exclusively in one organic solvent or a mixture of two or more organic solvents. This results in significant advantages over the processes of the prior art: as a result of the synchronism of diazotization and decomposition of the diazonium salt, the apparatus and time expenditure for the separate preparation of the diazonium salt solutions is unnecessary. In addition, a particularly favourable space-time yield is obtained and wastewater is produced only in the form of water of reaction.
It is regarded as particularly surprising and could not have been derived from the prior art that the diazotization of the anilines or amino-substituted pyridines of the formula (II) and the simultaneous reaction of the resulting diazonium salts to give sulphonyl chlorides can be achieved in a mixture of sulphur dioxide, hydrogen chloride, copper catalyst and organic solvents in high yield. It is known from the prior art that the diazonium salt which decomposes could react with the unreacted aniline to give undesired secondary products ((Houben-Weyl, Methoden der organischen Chemie [Methods in Organic Chemistry], 4th Edition, volume X/3, page 700). This phenomenon however does not arise in the process of the invention.
The sulphonyl chlorides can be isolated from the resulting reaction mixtures very easily. If the reaction has been carried out in an organic solvent which is miscible with water to an unlimited extent, then the water of reaction separates off with the copper salt used as catalyst as its own phase. If necessary, this phase separation is induced by adding small amounts of water. The excess of sulphur dioxide and hydrogen chloride is then driven off from the organic phase which remained. The sulphonyl chloride in the organic phase can then be further converted directly, for example, to give sulphonamides by reaction with ammonia or amines.